The Prostate最新文献

{"title":"Alcohol dehydrogenase expression patterns in normal prostate, benign prostatic hyperplasia, and prostatic adenocarcinoma in African American and Caucasian men.","authors":"Sarah A Stamis, Elisabeth I Heath, Steven Lucas, Julie Boerner, Leslie B Slusher","doi":"10.1002/pros.24310","DOIUrl":"10.1002/pros.24310","url":null,"abstract":"<p><strong>Background: </strong>In situ metabolism of ethanol by alcohol dehydrogenases (ADHs) contributes to oxidative damage of cells and DNA and has been linked to carcinogenesis in numerous epithelial tissues. The goal of this study was to determine expression patterns of ADH1 and ADH7 isozymes in normal, hyperplastic (benign prostatic hyperplasia [BPH]) and neoplastic (prostate cancer [PCa]) prostate. Furthermore, racial differences in ADH expression between African Americans and Caucasians were investigated.</p><p><strong>Methods: </strong>ADH expression patterns were characterized by density analysis of ADH immunohistochemistry (n = 21) and real-time RT-PCR of total RNAs by laser-capture microdissection (n = 10) and whole tissue formalin-fixed paraffin embedded prostate biopsies (n = 63).</p><p><strong>Results: </strong>ADH protein is found in normal prostate and is primarily associated with glandular epithelium. Transcripts of ADH1B are suppressed in PCa compared to BPH (p = 0.0095). Racial differences in ADH7 transcripts exist between African American and Caucasian men. A total of 57.6% of biopsies from African American prostates have detectable ADH7 messenger RNA (mRNA) transcripts compared to the 13.3% of Caucasian prostate biopsies with detectable transcripts (p = 0.0005). This increased frequency of detection contributes to higher mean ADH7 mRNA transcript levels in African Americans (p = 0.001).</p><p><strong>Conclusions: </strong>To our knowledge this study is the first to report downregulation of ADH1B in neoplastic prostate at the transcriptional level, suggesting protective regulatory functions. ADH7 transcripts were not detectable in all samples and was found in higher frequency and amount in our African American samples. Racial differences in ADH7 within the prostate is a novel finding and should be investigated further.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"666-675"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39596415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence trained with integration of multiparametric MR-US imaging data and fusion biopsy trajectory-proven pathology data for 3D prediction of prostate cancer: A proof-of-concept study.","authors":"Masatomo Kaneko,&nbsp;Norio Fukuda,&nbsp;Hitomi Nagano,&nbsp;Kaori Yamada,&nbsp;Kei Yamada,&nbsp;Eiichi Konishi,&nbsp;Yoshinobu Sato,&nbsp;Osamu Ukimura","doi":"10.1002/pros.24321","DOIUrl":"https://doi.org/10.1002/pros.24321","url":null,"abstract":"<p><strong>Background: </strong>We aimed to develop an artificial intelligence (AI) algorithm that predicts the volume and location of clinically significant cancer (CSCa) using convolutional neural network (CNN) trained with integration of multiparametric MR-US image data and MRI-US fusion prostate biopsy (MRI-US PBx) trajectory-proven pathology data.</p><p><strong>Methods: </strong>Twenty consecutive patients prospectively underwent MRI-US PBx, followed by robot-assisted radical prostatectomy (RARP). The AI algorithm was trained with the integration of MR-US image data with a MRI-US PBx trajectory-proven pathology. The relationship with the 3D-cancer-mapping of RARP specimens was compared between AI system-suggested 3D-CSCa mapping and an experienced radiologist's suggested 3D-CSCa mapping on MRI alone according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2. The characteristics of detected and undetected tumors at AI were compared in 22,968 image data. The relationships between CSCa volumes and volumes predicted by AI as well as the radiologist's reading based on PI-RADS were analyzed.</p><p><strong>Results: </strong>The concordance of the CSCa center with that in RARP specimens was significantly higher in the AI prediction than the radiologist' reading (83% vs. 54%, p = 0.036). CSCa volumes predicted with AI were more accurate (r = 0.90, p < 0.001) than the radiologist's reading. The limitations include that the elastic fusion technology has its own registration error.</p><p><strong>Conclusions: </strong>We presented a novel pilot AI algorithm for 3D prediction of PCa. AI was trained by integration of multiparametric MR-US image data and fusion biopsy trajectory-proven pathology data. This deep learning AI model may more precisely predict the 3D mapping of CSCa in its volume and center location than a radiologist's reading based on PI-RADS version 2, and has potential in the planning of focal therapy.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"793-803"},"PeriodicalIF":2.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39640624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protease-activated receptor-2 dependent and independent responses of bone cells to prostate cancer cell secretory products.","authors":"Charles N Pagel,&nbsp;Pamu K Kularathna,&nbsp;Reza Sanaei,&nbsp;Neil D Young,&nbsp;John D Hooper,&nbsp;Eleanor J Mackie","doi":"10.1002/pros.24316","DOIUrl":"https://doi.org/10.1002/pros.24316","url":null,"abstract":"<p><strong>Background: </strong>Metastatic prostate cancer lesions in the skeleton are frequently characterized by excessive formation of bone. Prostate cancer cells secrete factors, including serine proteases, that are capable of influencing the behavior of surrounding cells. Some of these proteases activate protease-activated receptor-2 (PAR₂ ), which is expressed by osteoblasts (bone-forming cells) and precursors of osteoclasts (bone-resorbing cells). The aim of the current study was to investigate a possible role for PAR₂ in regulating the behavior of bone cells exposed to metastatic prostate cancer cells.</p><p><strong>Methods: </strong>The effect of medium conditioned by the PC3, DU145, and MDA-PCa-2b prostate cancer cell lines was investigated in assays of bone cell function using cells isolated from wildtype and PAR₂ -null mice. Osteoclast differentiation was assessed by counting tartrate-resistant acid phosphatase-positive multinucleate cells in bone marrow cultured in osteoclastogenic medium. Osteoblasts were isolated from calvariae of neonatal mice, and BrdU incorporation was used to assess their proliferation. Assays of alkaline phosphatase activity and quantitative PCR analysis of osteoblastic gene expression were used to assess osteoblast differentiation. Responses of osteoblasts to medium conditioned by MDA-PCa-2b cells were analyzed by RNAseq.</p><p><strong>Results: </strong>Conditioned medium (CM) from all three cell lines inhibited osteoclast differentiation independently of PAR₂ . Media from PC3 and DU145 cells had no effect on assays of osteoblast function. Medium conditioned by MDA-PCa-2b cells stimulated BrdU incorporation in both wildtype and PAR₂ -null osteoblasts but increased alkaline phosphatase activity and Runx2 and Col1a1 expression in wildtype but not PAR₂ -null cells. Functional enrichment analysis of RNAseq data identified enrichment of multiple gene ontology terms associated with lysosomal function in both wildtype and PAR₂ -null cells in response to MDA-PCa-2b-CM. Analysis of individual genes identified osteogenesis-associated genes that were either upregulated by MDA-PCa-2b-CM selectively in wildtype cells or downregulated selectively in PAR₂ -null cells.</p><p><strong>Conclusions: </strong>Factors secreted by prostate cancer cells influence bone cell behavior through both PAR₂ -dependent and -independent mechanisms. Both PAR₂ -independent suppression of osteoclast differentiation and PAR₂ -dependent stimulation of osteogenesis are likely to determine the nature of prostate cancer metastases in bone.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"723-739"},"PeriodicalIF":2.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39925987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neighborhood deprivation and risk of mortality among men with prostate cancer: Findings from a long-term follow-up study.","authors":"Madhav K C,&nbsp;Evrim Oral,&nbsp;Ariane L Rung,&nbsp;Edward J Trapido,&nbsp;Laura S Rozek,&nbsp;Elizabeth T H Fontham,&nbsp;Jeannette T Bensen,&nbsp;Laura Farnan,&nbsp;Susan E Steck,&nbsp;Lixin Song,&nbsp;James L Mohler,&nbsp;Edward S Peters","doi":"10.1002/pros.24320","DOIUrl":"https://doi.org/10.1002/pros.24320","url":null,"abstract":"<p><strong>Background: </strong>The overall survival rate of prostate cancer (PCa) has improved over the past decades. However, huge socioeconomic and racial disparities in overall and prostate cancer-specific mortality exist. The neighborhood-level factors including socioeconomic disadvantage and lack of access to care may contribute to disparities in cancer mortality. This study examines the impact of neighborhood deprivation on mortality among PCa survivors.</p><p><strong>Methods: </strong>North Carolina-Louisiana Prostate Cancer Project (PCaP) data were used. A total of 2113 men, 1046 AA and 1067 EA, with PCa were included in the analysis. Neighborhood deprivation was measured by the Area Deprivation Index (ADI) at the census block group level using data from the US Census Bureau. Quintiles of ADI were created. Cox proportional hazards and competing risk models with mixed effects were performed to estimate the effect of neighborhood deprivation on all-cause and PCa-specific mortality adjusted for age, race, study site, insurance status, and comorbidities.</p><p><strong>Results: </strong>Participants living in the most deprived neighborhoods had an increased risk for all-cause mortality (quintiles 4 + 5: adjusted hazard ratio [aHR] = 1.51, 95% confidence interval [CI] = 1.16-1.96) compared to those in the least deprived (quintile 1) neighborhoods. The risk of prostate cancer-specific mortality was also higher among those living in the deprived neighborhoods (quintiles 4 + 5: aHR = 1.90, 95% CI = 1.10-3.50) than those in the least deprived neighborhood.</p><p><strong>Conclusions: </strong>The findings suggest neighborhood-level resources or health interventions are essential to improve survival among men with PCa. Additional research should focus on the mechanisms of how the neighborhood environment affects mortality.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"783-792"},"PeriodicalIF":2.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/21/c3/PROS-82-783.PMC9306458.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39950815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-organ confined stage and upgrading rates in exclusive PSA high-risk prostate cancer patients.","authors":"Benedikt Hoeh,&nbsp;Rocco S Flammia,&nbsp;Lukas Hohenhorst,&nbsp;Gabriele Sorce,&nbsp;Francesco Chierigo,&nbsp;Zhe Tian,&nbsp;Fred Saad,&nbsp;Michele Gallucci,&nbsp;Alberto Briganti,&nbsp;Carlo Terrone,&nbsp;Shahrokh F Shariat,&nbsp;Markus Graefen,&nbsp;Derya Tilki,&nbsp;Luis A Kluth,&nbsp;Philipp Mandel,&nbsp;Andreas Becker,&nbsp;Felix K H Chun,&nbsp;Pierre I Karakiewicz","doi":"10.1002/pros.24313","DOIUrl":"https://doi.org/10.1002/pros.24313","url":null,"abstract":"The pathological stage of prostate cancer with high‐risk prostate‐specific antigen (PSA) levels, but otherwise favorable and/or intermediate risk characteristics (clinical T‐stage, Gleason Grade group at biopsy [B‐GGG]) is unknown. We hypothesized that a considerable proportion of such patients will exhibit clinically meaningful GGG upgrading or non‐organ confined (NOC) stage at radical prostatectomy (RP).","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"687-694"},"PeriodicalIF":2.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39942341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of antisense oligonucleotides for splice-correction of androgen receptor pre-mRNA in castration-resistant prostate cancer models using cell-penetrating peptides.","authors":"Maria V Luna Velez,&nbsp;Omar Paulino da Silva Filho,&nbsp;Gerald W Verhaegh,&nbsp;Onno van Hooij,&nbsp;Najoua El Boujnouni,&nbsp;Roland Brock,&nbsp;Jack A Schalken","doi":"10.1002/pros.24309","DOIUrl":"https://doi.org/10.1002/pros.24309","url":null,"abstract":"<p><strong>Background: </strong>Cell-penetrating peptides (CPPs) are a promising approach for delivering antisense oligonucleotides (AONs) as they form nanosized complexes through noncovalent interactions that show efficient cellular uptake. Previously, we have designed an AON system to correct splicing of the androgen receptor (AR) pre-mRNA, thereby preventing the generation of the splice variant AR-V7 mRNA. AON-mediated knockdown of AR-V7 resulted in inhibition of androgen-independent cell proliferation. In this study, we evaluated the CPP-mediated delivery of this AON into castration-resistant prostate cancer cell line models 22Rv1, DuCaP (dura mater cancer of the prostate), and VCaP (vertebral cancer of the prostate).</p><p><strong>Methods: </strong>Nanoparticles (polyplexes) of AONs and CPPs were formed through rapid mixing. The impact of the peptide carrier, the formulation parameters, and cell incubation conditions on cellular uptake of fluorescently labeled AONs were assessed through flow cytometry. The cytotoxic activity of these formulations was measured using the CellTiter-Glo cell viability assay. The effectivity of CPP-mediated delivery of the splice-correcting AON-intronic splicing enhancer (ISE) targeting the ISE in the castration-resistant prostate cancer (CRPC)-derived 22Rv1, DuCaP, and VCaP cells was determined by measuring levels of AR-V7 mRNA normalized to those of the human heterochromatin protein 1 binding protein 3 (HP1BP3). Western blot analysis was used to confirm AR-V7 downregulation at a protein level. The cellular distribution of fluorescently labeled AON delivered by a CPP or a transfection reagent was determined through confocal laser scanning microscopy.</p><p><strong>Results: </strong>The amphipathic and stearylated CPP PepFect 14 (PF14) showed higher uptake efficiency than arginine-rich CPPs. Through adjustment of formulation parameters, concentration and incubation time, an optimal balance between carrier-associated toxicity and delivery efficiency was found with a formulation consisting of an amino/phosphate ratio of 3, 0.35 μM AON concentration and 30 min incubation time of the cells with polyplexes. Cellular delivery of AON-ISE directed against AR pre-mRNA achieved significant downregulation of AR-V7 by 50%, 37%, and 59% for 22Rv1, DuCaP, and VCaP cells, respectively, and reduced androgen-independent cell proliferation of DuCaP and VCaP cells.</p><p><strong>Conclusions: </strong>This proof-of-principle study constitutes the basis for further development of CPP-mediated delivery of AONs for targeted therapy in prostate cancer.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"657-665"},"PeriodicalIF":2.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39574286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of cycling and rowing on serum concentrations of prostate-specific antigen: A randomized study of 101 male subjects.","authors":"Andreas Lunacek,&nbsp;Mathias Tischler,&nbsp;Christof Mrstik,&nbsp;Doris Hebenstreit,&nbsp;Reinhard Oeser,&nbsp;Jasmin Bektic,&nbsp;Helmut Klocker,&nbsp;Wolfgang Horninger,&nbsp;Eugen Plas","doi":"10.1002/pros.24322","DOIUrl":"https://doi.org/10.1002/pros.24322","url":null,"abstract":"<p><strong>Objective: </strong>To determine the effects if cycling and rowing on serum prostate-specific antigen (PSA) levels.</p><p><strong>Methods: </strong>Male volunteers (n = 101), aged 20-80 (mean, 49.9) years were randomized to exercise at the first or second study visit. They performed 1 h of either cycling or rowing on a stationary machine. To determine exercise-induced effects on the PSA level, serum total PSA (tPSA) and free PSA (fPSA) concentrations were evaluated before and after exercise and another sampling was performed at the second study visit. Pre-exercise and postexercise tPSA and fPSA concentrations were compared using the Wilcoxon matched-pairs test. The results were analyzed using the Mann-Whitney U-test.</p><p><strong>Results: </strong>A significant (p < 0.001) average increase in tPSA after exercise (1.14 ± 1.11 ng/ml to 1.24 ± 1.26 ng/ml [mean, +8.8%]) was observed after both cycling and rowing, without significant differences between the sports (p = 0.54). The exercise-induced increase in PSA concentration affected participants aged ≥50 years (difference, 0.16 ± 0.37; p < 0.001), but not those aged <50 years (difference, 0.01 ± 0.06; p = 0.23). The effect size was clinically irrelevant in all except two outliers, in whom a distinct increase of PSA level by averages of 1.80 ng/ml (+55%) for tPSA and 1.25 ng/ml (+227%) for fPSA following cycling was observed.</p><p><strong>Conclusion: </strong>Rowing and cycling generally do not have a clinically relevant effect on PSA levels. However, outliers exist. Our findings do not support abstaining from exercise during the days approaching PSA sampling.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"804-808"},"PeriodicalIF":2.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39653988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplex immunohistochemical phenotyping of T cells in primary prostate cancer.","authors":"Busra Ozbek,&nbsp;Onur Ertunc,&nbsp;Andrew Erickson,&nbsp;Igor D Vidal,&nbsp;Carolina Gomes-Alexandre,&nbsp;Gunes Guner,&nbsp;Jessica L Hicks,&nbsp;Tracy Jones,&nbsp;Janis M Taube,&nbsp;Karen S Sfanos,&nbsp;Srinivasan Yegnasubramanian,&nbsp;Angelo M De Marzo","doi":"10.1002/pros.24315","DOIUrl":"https://doi.org/10.1002/pros.24315","url":null,"abstract":"<p><strong>Background: </strong>Most prostate cancers are \"immune cold\" and poorly responsive to immune checkpoint inhibitors. However, the mechanisms responsible for the lack of a robust antitumor adaptive immune response in the prostate are poorly understood, which hinders the development of novel immunotherapeutic approaches.</p><p><strong>Aims: </strong>Most inflammatory infiltrates in the prostate are centered around benign glands and stroma, which can confound the molecular characterization of the antitumor immune response. We sought to analytically validate a chromogenic-based multiplex immunohistochemistry (IHC) approach applicable to whole slide digital image analysis to quantify T cell subsets from the tumor microenvironment of primary prostatic adenocarcinomas. As an initial application, we tested the hypothesis that PTEN loss leads to an altered antitumor immune response by comparing matched regions of tumors within the same individual with and without PTEN loss.</p><p><strong>Materials & methods: </strong>Using the HALO Image Analysis Platform (Indica Labs), we trained a classifier to quantify the densities of eight T cell phenotypes separately in the tumor epithelial and stromal subcompartments.</p><p><strong>Results: </strong>The iterative chromogenic approach using 7 different antibodies on the same slide provides highly similar findings to results using individually stained slides with single antibodies. Our main findings in carcinomas (benign removed) include the following: i) CD4+ T cells are present at higher density than CD8+ T cells; ii) all T cell subsets are present at higher densities in the stromal compartment compared to the epithelial tumor compartment; iii) most CD4+ and CD8+ T cells are PD1+; iv) cancer foci with PTEN loss harbored increased numbers of T cells compared to regions without PTEN loss, in both stromal and epithelial compartments; and v) the increases in T cells in PTEN loss regions were associated with ERG gene fusion status.</p><p><strong>Discussion: </strong>This modular approach can apply to any IHC-validated antibody combination and sets the groundwork for more detailed spatial analyses.</p><p><strong>Conclusion: </strong>Iterative chromogenic IHC can be used for whole slide analysis of prostate tissue samples and can complement transcriptomic results including those using single cell and spatial genomic approaches.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"706-722"},"PeriodicalIF":2.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39638360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ductal and acinar components of mixed prostatic adenocarcinoma frequently have a common clonal origin.","authors":"Claes Lindh,&nbsp;Hemamali Samaratunga,&nbsp;Brett Delahunt,&nbsp;Rebecka Bergström,&nbsp;Venkatesh Chellappa,&nbsp;John Yaxley,&nbsp;Johan Lindberg,&nbsp;Lars Egevad","doi":"10.1002/pros.24304","DOIUrl":"https://doi.org/10.1002/pros.24304","url":null,"abstract":"<p><strong>Background: </strong>Ductal adenocarcinoma (DA) is an aggressive subtype of prostate cancer. It is most commonly seen in mixed tumors together with conventional acinar adenocarcinoma (AA). The genetic profile of DA and its clonal origin is not fully characterized.</p><p><strong>Objective: </strong>To investigate whether DA represents a distinct genetic subtype and to investigate the somatic relationship between the ductal and acinar components of mixed cancers.</p><p><strong>Design, setting, and participants: </strong>In 17 radical prostatectomy specimens ductal and acinar tumor components from the same tumor foci were dissected. DNA was extracted and genomic sequencing performed. After exclusion of two cases with low cell yield, 15 paired samples remained for analysis.</p><p><strong>Results: </strong>In 12 of 15 cases a common somatic denominator was identified, while three cases had clonally separate components. In DA, TMPRSS2-ERG gene fusions were detected in 47% (7/15), clonal FOXA1 alterations in 33% (5/15) and SPOP alterations in 27% (4/15) of cases. In one case KIAA1549-BRAF fusion was identified. Genome doubling events, resulting in an increased ploidy, were identified in the DA in 53% (8/15) of cases, but not seen in any AA. PTEN and CTNNB1 alterations were enriched in DA (6/15) but not seen in any AA. No cancers showed microsatellite instability or high tumor mutation burden.</p><p><strong>Conclusions: </strong>Ductal and acinar prostate adenocarcinoma components of mixed tumors most often share the same origin and are clonally related. DA components in mixed tumor often exhibit genome doubling events resulting in aneuploidy, consistent with the aggressive nature of high grade prostate cancer.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"576-583"},"PeriodicalIF":2.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/68/b3/PROS-82-576.PMC9306900.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39835970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a nomogram combining multiparametric magnetic resonance imaging and PSA-related parameters to enhance the detection of clinically significant cancer across different region.","authors":"Zhien Zhou,&nbsp;Zhen Liang,&nbsp;Yuzhi Zuo,&nbsp;Yi Zhou,&nbsp;Weigang Yan,&nbsp;Xingcheng Wu,&nbsp;Zhigang Ji,&nbsp;Hanzhong Li,&nbsp;Mengyao Hu,&nbsp;Lin Ma","doi":"10.1002/pros.24302","DOIUrl":"https://doi.org/10.1002/pros.24302","url":null,"abstract":"<p><strong>Objective: </strong>Prostate cancer (PCa) is the most prevalent cancer among males. This study attempted to develop a clinically significant prostate cancer (csPCa) risk nomogram including Prostate Imaging-Reporting and Data System (PI-RADS) score and other clinical indexes for initial prostate biopsy in light of the different prostate regions, and internal validation was further conducted.</p><p><strong>Patients and methods: </strong>A retrospective study was performed including 688 patients who underwent ultrasound-guided transperineal magnetic resonance imaging fusion prostate biopsy from December 2016 to July 2019. We constructed nomograms combining PI-RADS score and clinical variables (prostate-specific antigen [PSA], prostate volume (PV), age, free/total PSA, and PSA density) through univariate and multivariate logistic regression to identify patients eligible for biopsy. The performance of the predictive model was evaluated by bootstrap resampling. The area under the curve (AUC) of the receiver-operating characteristic (ROC) analysis was appointed to quantify the accuracy of the primary nomogram model for csPCa. Calibration curves were used to assess the agreement between the biopsy specimen and the predicted probability of the new nomogram. The χ² test was also applied to evaluate the heterogeneity between fusion biopsy and systematic biopsy based on different PI-RADS scores and prostate regions.</p><p><strong>Results: </strong>A total of 320 of 688 included patients were diagnosed with csPCa. csPCa was defined as Gleason score ≥7. The ROC and concordance-index both presented good performance. The nomogram reached an AUC of 0.867 for predicting csPCa at the peripheral zone; meanwhile, AUC for transitional and apex zones were 0.889 and 0.757, respectively. Statistical significance was detected between fusion biopsy and systematic biopsy for PI-RADS score >3 lesions and lesions at the peripheral and transitional zones.</p><p><strong>Conclusion: </strong>We produced a novel nomogram predicting csPCa in patients with suspected imaging according to different locations. Our results indicated that PI-RADS score combined with other clinical parameters showed a robust predictive capacity for csPCa before prostate biopsy. The new nomogram, which incorporates prebiopsy data including PSA, PV, age, and PI-RADS score, can be helpful for clinical decision-making to avoid unnecessary biopsy.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"556-565"},"PeriodicalIF":2.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39736164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}